crossing96/oncoscreening huggingface dataset:
Impact of the controlling nutritional status (CONUT) score on perioperative morbidity and oncological outcomes in patients with bladder cancer treated with radical cystectomy.	INTRODUCTION AND OBJECTIVES: To evaluate the impact of the Controlling Nutritional Status (CONUT) score on perioperative morbidity and oncological outcomes of bladder cancer (BC) patients treated with radical cystectomy (RC). MATERIALS AND METHODS: We retrospectively analyzed a multi-institutional cohort of 347 patients treated with RC for clinical-localized BC between 2005 and 2019. The CONUT-score was defined as an algorithm including serum albumin, total lymphocyte count, and cholesterol. Multivariable logistic regression analyses were performed to evaluate the ability of the CONUT-score to predict any-grade complications, major complications and 30 days readmission. Multivariable Cox' regression models were performed to evaluate the prognostic effect of the CONUT-score on recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS). RESULTS: A cut-off value to discriminate between low and high CONUT-score was determined by calculating the receiver operating characteristic (ROC) curve. The area under the curve was 0.72 hence high CONUT-score was defined as ≥3 points. Overall, 112 (32.3%) patients had a high CONUT. At multivariable logistic regression analyses, high CONUT was associated with any-grade complications (OR 3.58, P = 0.001), major complications (OR 2.56, P = 0.003) and 30 days readmission (OR 2.39, P = 0.01). On multivariable Cox' regression analyses, high CONUT remained associated with worse RFS (HR 2.57, P < 0.001), OS (HR 2.37, P < 0.001) and CSS (HR 3.52, P < 0.001). CONCLUSIONS: Poor nutritional status measured by the CONUT-score is independently associated with a poorer postoperative course after RC and is predictive of worse RFS, OS, and CSS. This simple index could serve as a comprehensive personalized risk-stratification tool identifying patients who may benefit from an intensified regimen of supportive cares.	bladder
Analysis of sex-based differences to Bacillus Calmette-Guérin for non-muscle invasive bladder cancer.	OBJECTIVE: To evaluate whether differences exist between men and women in response to intravesical BCG treatments. The incidence of urothelial carcinoma of the bladder is lower in women but they tend to present with more aggressive and advanced disease. Some prior studies also suggest there are sex-based differences in response to treatment for non-muscle invasive bladder tumors. METHODS: In this retrospective study, we reviewed all consecutive patients who received BCG at the CHU de Québec - Laval University from 2009-2019. Men and women were treated with intravesical BCG therapy following pathologic confirmation of urothelial carcinoma. Outcomes evaluated include recurrence, progression, and treatment tolerability. Recurrence was defined as a pathology confirmed cancer whereas progression was the new development of high-grade (recurrence) pathology or an increase of stage. Tolerability was defined according to the proportion of prescribed BCG received. All clinical details were obtained through review of the medical records, collaborated by pharmacy records for BCG administration. Competing-risk analysis was used to compare outcomes. RESULTS: Among 613 patients who received BCG at our institution between 2009-2019, 472 (77.0%) were men and 141 (23.0%) were women. The recurrence rate was not different between sexes, with a 5-year recurrence risk of 52% (95% CI: 36.93-65.4) among women compared to 57.5% (CI 95%: 51.9-62.6) among men. The overall non-progression rate at 1,3 and 5 years was 97.3% (95% CI: 95.6%-98.3%), 93.6% (95% CI: 91.2%-95.4%), and 91.7% (95% CI: 88.4%-94.1%), respectively. The completion of ≥5 induction BCG instillations and maintenance BCG use was similar in both genders. CONCLUSIONS: We report a contemporary NMIBC cohort treated with BCG and find no clear evidence for sex-based differences in response to BCG treatment in regard of progression, recurrence, and tolerability.	bladder
Is Robotic Superior to Laparoscopic Approach for Radical Nephroureterectomy with Bladder Cuff Excision in Treating Upper Urinary Tract Urothelial Carcinoma?	Background: Laparoscopic nephroureterectomy (LNU) has become popular in treating upper urinary tract urothelial carcinoma (UTUC) and an emerging trend was observed in robotic approaches. Therefore, we compared robot-assisted radical nephroureterectomy (RANU) and LNU for the treatment of UTUC. Materials and Methods: This observational and retrospective case-series study included UTUC patients who underwent LNU or RANU. A pure laparoscopic approach was adopted in the LNU treatment group, and bladder cuff excision (BCE) was performed mostly with the open approach. Either the da Vinci Si or Xi surgical system was used for RANU. Extravesical BCE was performed, and bladder defects were closed intracorporeally. Perioperative and oncologic outcomes were compared between the LNU and RANU groups. Results: A total of 231 patients who underwent RANU (n = 87) or LNU (n = 144) were included. No significant differences were noted between the groups in terms of demographics, tumor characteristics, operative time, catheter time, or complications. Compared with LNU, RANU had a lower intraoperative blood loss (30 vs. 150 mL, p < 0.001) and shorter postoperative hospital stay (8 vs. 9 days, p = 0.009). The 5-year overall survival, cancer-specific survival, and bladder recurrence-free survival were comparable between the groups. Conclusion: Compared with LNU, RANU had similar perioperative and oncologic outcomes but was superior in terms of intraoperative blood loss and postoperative length of hospital stay. However, considering the potential biases owing to the heterogeneity of our cases, the interpretation of the results must be very cautious.	bladder
Biology of BCG response in non-muscle invasive bladder cancer - 2021 IBCN Updates Part III.	Bacillus Calmette-Guerin (BCG) remains the only FDA-approved first-line therapy in patients with high-risk non-muscle invasive bladder cancer. Recurrences, even after adequate BCG therapy, are common and the efficacy of second-line therapies remains modest. Therefore, early identification of patients likely to recur and treatment after recurrence remain critical unmet needs in the clinical care of bladder cancer patients. To address these deficits, a better understanding of the mechanisms of resistance to BCG-therapy is needed. The virtual update of the International Bladder Cancer Network (IBCN) on the biology of response to BCG focused on potential mechanisms and markers of resistance to intravesical BCG therapy. The insights from this meeting will be highlighted and put into context of previously reported mechanisms of resistance to BCG in this review.	bladder
Evaluation of toxicities for intravesical drugs in phase 1 bladder cancer trials.	BACKGROUND: Improving clinical trial design is important for optimizing approval of safe and effective drugs. Phase 1 clinical trials seek to determine phase 2 doses by investigating predefined dose-limiting toxicities. Traditional definitions of dose-limiting toxicity may not be applicable to intravesical therapies for bladder cancer. This study compared the frequency of dose-limiting toxicities and serious adverse events in bladder cancer trials for intravesical therapies to other routes of administration. METHODS: Studies were abstracted from ClinicalTrials.gov and reconciled with a PubMed search. Primary and secondary end points were predefined before data abstraction, and the primary end point was subject-level dose-limiting toxicity rate. Fisher exact tests were performed with p < .05 designated as significant. RESULTS: Eighteen intravesical studies and 24 studies with other routes of administration (the per os/intravenous/intramuscular [PO/IV/IM] group) were identified. Dose-limiting toxicities were reported in 38.9% of intravesical studies, affecting 3.29% of subjects, compared with 30.0% of PO/IV/IM studies representing 4.19% of subjects (p = .52 for study-level and p = .60 for subject-level comparisons). Serious adverse events occurred in 53.9% of intravesical studies in 10.3% of subjects versus 91.0% of studies reporting serious adverse events affecting 41.4% of subjects in the PO/IV/IM group (p = .03 for subject-level and p < .0001 for study-level comparisons). CONCLUSIONS: There was no difference in subject-level dose-limiting toxicity rate between intravesical and PO/IV/IM bladder cancer trials. The serious adverse event rate was lower in the intravesical group. Heterogeneity of dose-limiting toxicity definition may affect interpretation of toxicity in phase 1 bladder cancer clinical trials studying different routes of administration. LAY SUMMARY: Bladder cancer is a common cancer type that may be treated with therapies that are instilled into the bladder and act locally, called intravesical therapies. This study used publicly available regulatory data from early phase clinical trials to determine whether measures of tolerability used in clinical trials are applicable to intravesical therapies for bladder cancer.	bladder
Sphingosine Kinase 1 Acts as a Hypoxia-Upregulated Oncogene to Regulate Cell Invasion and Resistance to NK Cell Killing in Bladder Carcinoma Cells.	OBJECTIVE: Hypoxia facilitates an aggressive phenotype and immune evasion in solid tumors including bladder cancer (BC). Sphingosine kinase 1 (SphK1) is aberrantly expressed and correlated with poor prognosis in BC patients. However, its roles in hypoxia-evoked malignancies and immune evasion in BC remain elusive. METHODS: The expression of SphK1 in BC tissues was analysed using a bioinformatics database. BC cells were transfected with si-SphK1 or recombinant HIF-1α plasmids under hypoxic conditions. The mRNA level, activity and protein expression of SphK1 were determined. Transwell assay was performed to evaluate cell invasion. After co-culture with natural killer (NK) cells, NK cell cytotoxicity to BC cells was assessed. The involvement of sphingosine-1-phosphate (S1P)/HIF-1α signaling was analysed by ELISA, qRT-PCR and western blot. RESULTS: UALCAN and GEPIA database confirmed high expression of SphK1 in BC tissues. Moreover, hypoxia increased the expression and activity of SphK1. Loss of SphK1 inhibited hypoxia-induced cell invasion. IL-2 induced NK cell activation by secreting TNF-α and IFN-γ. Hypoxia antagonized NK cell activation-evoked cytotoxicity to BC cells. Intriguingly, SphK1 knockdown reversed hypoxia-induced cell resistance to NK cell killing. Mechanically, SphK1 loss inhibited hypoxia-activated the S1P/HIF-1α signaling. However, S1P addition reversed the inhibitory effects of SphK1 down-regulation on hypoxia-activated S1P/HIF-1α signaling. Notably, reactivating HIF-1α overturned the suppressive roles of SphK1 loss in decreasing hypoxia-induced cell invasion and resistance to NK cell cytotoxicity. CONCLUSIONS: Targeting SphK1 may inhibit hypoxia-evoked invasion and immune evasion via the S1P/HIF-1α signaling, indicating a promising therapeutic target for BC.	bladder
In vitro cytotoxicity of human urine and its potential toxic parameters towards bladder cancer cells.	BACKGROUND: Bladder cancer (CaB) has a high recurrence rate despite surgery. As bladder is constantly filled with urine, it is worthwhile to investigate whether it could have any detrimental effects on bladder cancer cells. METHODS: We investigated the cytotoxicity of urine samples from CaB patients and normal controls on four CaB cell lines and tested the percentage of cell death, proliferation, adhesion, invasion and colonies formation ability. In order to identify the potential components involving in urine cytotoxicity, we evaluated some basic physiochemical parameters of urines, such as pH, osmolarity, creatinine (Cr), sodium (Na), potassium (K), chloride (Cl), calcium (Ca) and phosphate (PO4). We further compared the pH values of urine samples between CaB who developed recurrence versus those who did not. A more in-depth analysis on inflammatory markers was performed for two representative urine samples which demonstrated opposite cytoxic effects. RESULTS: 23 CaB patients and 20 normal controls were recruited into this study. According to in vitro experiments, both CaB and non-CaB urines had comparable effect on cell toxicity, proliferation, adhesion, invasion and colonies formation ability in four cell lines, HTB9, RT4, T24 and UMUC3, while RT4 was the most sensitive to urine toxicity. After evaluating the relationship between basic physiochemical parameters and cytotoxicity, we found out that there were strong negative correlations between pH value and 24 hours death rate for the 4 CaB cell lines (HTB9 r = -0.6651, p<0.001; RT4 r = -0.8335, p<0.001; T24 r = -0.4924, p<0.001; UMUC3 r = -0.7066, p<0.001). Osmolarity, urine Cr and PO4 all had weakly or moderately positive correlations with CaB cells on 24 hours death rate. CaB patients who developed recurrence had more alkaline urine than those who did not develop recurrence. In the urine sample with the highest cytoxicity, high concentrations of IL-6 and IFN-gamma were found. CONCLUSIONS: Our study confirmed that there was not statistically significant difference in cytotoxicity between CaB and non-CaB urines. However, we identified some parameters that could have an impact on cytotoxicity towards CaB cells. Modifying certain urine characteristics peri-operatively may induce cytotoxicity, avoid tumour re-implantation, and reduce the chance of cancer recurrence.	bladder
Discriminating bladder cancer cells through rheological mechanomarkers at cell and spheroid levels.	The stiffening or softening of cancers observed in nanoindentation experiments has been recognized as a marker of cancer-related changes. In bladder cancers, continuous stretching/destretching is observed due to its functionality, indicating that shear forces dominate the mechanical response of these cells. Thus, nanoindentation and microrheological measurements conducted in parallel allow for a fully reliable mechanomarker of cancer progression. Here, bladder cancer cell lines, i.e., non-malignant cell cancer of the ureter (HCV29), bladder carcinoma (HT1376), and transitional cell carcinoma (T24), were studied. Nanoindentation and microrheological experiments were conducted on individual cells, cell monolayers, and spheroids that were formed using non-adherent surface plates. The results show that nanoindentation experiments can only differentiate between non-malignant HCV29 (stiffer) and cancerous HT1376 and T24 (softer) cells. Applying microrheology recognizes the type of grade 3 bladder cancers (carcinoma HT1376 or transitional cell carcinoma T24 cells). We showed that actin filaments are a vital element defining the rheological properties of spheroids. Differences in mechanical properties of cell monolayers could be associated with thick actin bundles and intercellular connections, with some extracellular matrix (ECM) contributing to the stiffening of such monolayers. Our findings demonstrate that a complete image of how cancer cells respond to mechanical stress (compressive and shear forces) can only be obtained after microrheological measurements using the transition frequency separating elastic and viscous regimes as a non-labeled biomarker of bladder cancer progression.	bladder
Comparative cost-effectiveness of neoadjuvant chemotherapy regimens for muscle-invasive bladder cancer: Results according to VESPER data.	BACKGROUND: The VESPER trial demonstrated improved progression-free (PFS) and (preliminarily) overall survival (OS) with six cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVACx6) versus four cycles of gemcitabine and cisplatin (GCx4) before radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), but with increased toxicity. This study compares the cost-effectiveness of these regimens. METHODS: A cost-effectiveness analysis of neoadjuvant ddMVACx6 and GCx4 was performed using a decision-analytic Markov model with 5-year, 10-year, and lifetime horizons. Probabilities were derived from reported VESPER data. Utility values were obtained from the literature. Primary outcomes were effectiveness measured in quality-adjusted life years (QALY) and incremental cost-effectiveness ratio (ICER) with a willingness to pay threshold of $100,000 per QALY. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of the model. RESULTS: At 5 years, ddMVACx6 improved QALYs by 0.30 at an additional cost of $16,100, rendering it cost-effective relative to GCx4 (ICER: $53,284/QALY). Additionally, probabilistic sensitivity analysis found ddMVACx6 to be cost-effective in 79% and 81% of microsimulations at10-year and lifetime horizons, respectively. One-way sensitivity analysis demonstrated a minimum difference in 5-year progression of 0.9% and progression mortality of 0.7% between ddMVACx6 and GCx4 was necessary for ddMVACx6 to remain cost-effective. CONCLUSIONS: Neoadjuvant ddMVACx6 was more cost-effective than GCx4 for MIBC. These data, together with the improved PFS and (albeit preliminary) OS noted in VESPER, support use of this regimen in appropriate candidates for neoadjuvant chemotherapy before RC. LAY SUMMARY: We performed a benefit-to-cost analysis using evidence from a randomized controlled trial that compared two different chemotherapy treatments before bladder removal for bladder cancer that had invaded into the bladder muscle. Despite being more expensive and having a greater likelihood of toxicity, six cycles of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin was more cost-effective (or had higher value) than four cycles of gemcitabine and cisplatin.	bladder
Metabolic-associated signature and hub genes associated with immune microenvironment and prognosis in bladder cancer.	The relationship between metabolism and immune microenvironment remains to be studied in bladder cancer (BCa). We aimed to construct a metabolic-associated signature for prognostic prediction and investigate its relationship with the immune microenvironment in BCa. The RNA expression of metabolism associated genes was obtained from a combined data set including The Cancer Genome Atlas, GSE48075, and GSE13507 to divide BCa patients into different clusters. A metabolic-associated signature was constructed using the differentially expressed genes between clusters in the combined data set and validated in the IMvigor210 trial and our center. The composition of tumor-infiltrating immune cells (TIICs) was evaluated using the single-sample Gene Set Variation Analysis. BCa patients in Cluster A or high-risk level were associated with advanced clinicopathological features and poor survival outcomes. The percentage of high-risk patients was significantly lower in patients responding to anti-PD-L1 treatment. Compared with low-risk patients, the IC50 values of cisplatin and gemcitabine were significantly lower in high-risk patients. Thiosulfate transferase (TST) and S100A16 were significantly associated with clinicopathological features and prognosis. Downregulation of TST promoted BCa cell invasion, migration, and epithelial-to-mesenchymal transition, which are inhibited by downregulation of S100A16. CD8 + T cells, neutrophils, and dendritic cells had higher infiltration in the TST low-level and the S100A16 high-level. Furthermore, loss of function TST and S100A16 significantly affected the expression of PD-L1 and CD47. The metabolic-associated signature can stratify BCa patients into distinct risk levels with different immunotherapeutic susceptibility and survival outcomes. Metabolism disorder promoted the dysregulation of immune microenvironment, thus contributing to immunosuppression.	bladder
The tumor microenvironment and prognostic role of autophagy- and immune-related genes in bladder cancer.	BACKGROUND: Autophagy-related genes and immune-related genes contribute significantly to the initiation and prognosis of bladder cancer (BLCA). OBJECTIVE: We aimed to explore differentially expressed autophagy-related genes (DEARGs) and immune-related genes (DEIRGs) in BLCA to create a prognostic risk assessment model and gain some insights into BLCA's molecular underpinnings. METHODS: The prognostic DEARGs and DEIRGs were evaluated for BLCA through The Cancer Genome Atlas (TCGA) database (n= 399) and GSE13507 dataset (n= 165). The BLCA risk model was constructed and verified. The immune score, stromal score, and estimate score in different risk groups were calculated by the ESTIMATE algorithm. Immune infiltration levels were assessed by a single sample gene set enrichment analysis (GSEA) algorithm. RESULTS: In the risk model, AURKA, ACTC1, MYLK, PDGFD, PDGFRA and TNC were significantly associated with the overall survival. The pathways in cancer, T cell receptor signaling pathway and B cell receptor signaling pathway were significantly gathered in the high-risk group. Moreover, the risk score was significantly correlated with infiltrating immune cells, expression of critical immune checkpoints and mismatch repair genes including MSH6, MLH1, and MSH2. CONCLUSIONS: In this study, three DEARGs (AURKA, ACTC1, MYLK) and three DEIRGs (PDGFD, PDGFRA, TNC) were demonstrated to be potential prognostic biomarkers for BLCA patients through bioinformatics methods, which might be novel therapeutic targets and prognostic markers for BLCA, in follow up studies, we will combine experiments to verify this.	bladder
The effect of prior prostate cancer treatment on perioperative and pathological outcomes after cystectomy.	INTRODUCTION: A comprehensive analysis on outcomes in the perioperative and pathological setting in patients with a prior diagnosis of prostate cancer has not been performed. The objective of this study is to describe the effect of prior prostate cancer treatment on perioperative and pathological outcomes after cystectomy. MATERIALS AND METHODS: This was a retrospective review of all male patients who underwent cystectomy at our institution from 01/01/2007-01/01/2020. Patients who were previously diagnosed and treated for prostate cancer were identified and outcomes were assessed. RESULTS: In 525 male patients, 132 (25.1%) had a diagnosis of prostate cancer prior to cystectomy. In the patients with a history of prostate cancer, 59 (46.2%) patients underwent prior radical prostatectomy (RP), 52 (39.4%) underwent some form of radiation therapy and the remaining 21 were managed with other modalities, including 11.4% who were on active surveillance. When comparing perioperative outcomes, there were no significant differences in outcomes. Pathological outcomes revealed that pT4 disease was more common in the RT cohort (19.2%, p = 0.05). In patients with no history of prostate cancer, 151 (40.2%) were found to have incidental prostate cancer at the time of cystectomy. Most (67.5%) patients with incidental prostate cancer had Gleason < 7 disease and only 1.3% developed metastatic prostate cancer on follow up, compared to over 10% of the patients previously treated for prostate cancer (p < 0.05). CONCLUSIONS: Patients who underwent prostate cancer treatment prior to cystectomy may be at increased risk for worse perioperative and pathologic outcomes after cystectomy.	bladder